DESCRIPTION: This is a revised continuation proposal. The broad objectives are to develop applications of gradients and radiofrequency pulse shaping for nuclear resonance spectroscopy of biomolecules, particularly in concentrated solvents. The focus is on intermolecular multiple-quantum (iMQ) coherences and crosspeaks between proteins and water. Both the theoretical and experimental work will be continued on dilute solution of biomolecules in water. Specifically, the in vivo imaging and spectroscopy work will be extended with the aims of enhancing image contrast and validating proposed mechanisms for functional MRI. High resolution NMR at high fields will be pursued using magnets which give inhomogeneous field (e.g. the existing 27T and proposed 30T magnets at the NHMFL). Work on small-signal amplification by solute-solvent coherence transfer will also be pursued with the view of revolutionizing the way in which low-gamma or low-concentration species are detected in NMR. Suppression of iMQ coherences in sequences such TOCSY will be explored to produce improved versions.